Cell Injury and Adaptation

Cell injury 
Causes are 

• Hypoxia 
• Infections
• Immunologic reactions
• Congenital disorders 
• Chemical injury
• Physical injury
• Nutritional imbalance 

Hypoxia

• Deficiency of oxygen due to redn in blood flow.

Types:

• Anoxic or hypoxic
• Anemic 
• Cardiopulmonary failure
• Histotoxic 

Infections

• Bacterial 
• Viral 
• Protozoal 
• Fungal
• Proteins like prions induced disease

Immunological reactions 

• Also called hypersensitivity reaction.
• They are protective to our body, but when excess they can have collateral tissue damage.
• Autoimmune diseases are targetted to the body cells causing their destruction.

Types:

• Type I
• Type II
• Type III
• Type IV 

Congenital disorders 

Disease due to trisomy

• Down’s syndrome
• Patau synrome
• Edward syndrome

Disorders of sex chromosome 

• Klinefeter’s syndrome
• Turner’s syndrome

Autosomal recessive 

• Osteogenesis imperfecta
• Cystic fibrosis
• Alkaptonuria
• Phnylketonuria
• Glycogen and lysosome storage disease

Autosomal dominant

• Familial hypercholesterolemia
• Marfan syndrome
• Ehler Danlos syndrome
• Neurofibromatosis

X linked recessive

• Lysch nyhan syndrome
• Chronic granulomatous disease

X linked dominant

• Fragile X syndrome
• Huntingtons disease

Physical agent

• Heat
• Cold
• Radiation
• Burn
• Crush
• Gunshot 
• Pressure changes

Chemicals 

• Acid
• Alkali
• Cyanide
• Poisons like arsenic, lead, mercury
• Alcohol
• Cigarette smoking
• IV drug abuse 

Nutrition

PEM 

• Anorexia nervosa
• Kwarshiorker
• Marasmus

Vitamin deficiency

• Scurvy, beri beri, pellagra
• Anemia
• Subacute combined degeneration (vit B12)

Nutrition excess

• Obesity and related disorders

Tissue response 

Cellular changes during cell injury

Reversible cell injury 

• ATP depletion
• Glycolysis and acidosis
• Na/H2O influx and cell swelling
• Ribosomal detachment
• Plasma membrane blebs and myelin figures are seen

• If oxygen is available and the other noxious stimuli are removed the cell can recover. If not it will go into irreversible stage.

Irreversible cell injury hallmarks 

• Severe membrane damage
• Marked mitochondrial dysfunction
• Lysosomal rupture and cell autodigestion
• Nuclear changes 
• Condensation/ pyknosis 
• Fragmentation/ karyorrhexis
• Disappearance / karyolysis 

Finally it will lead to the cellular death and inflammation.

Tissue death/necrosis 

Morphologic types 

• Coagulative necrosis- due to ischemia, cells are dead but cellular architecture is preserved. Eg in solid organs like liver and kidney.
• Liquefactive necrosis- necrosed cells are partially digested by lysosomal enzymes, and hence the cellular architecture is lost revealing cheesy material. Eg in brain , abscess and spleen.
• Casseous necrosis- combination of these two types. Seen in granulomas like TB.
• Fat necrosis- in fatty tissue due to the release of lipase.
• Fibrinoid necrosis- with the deposition of non specific protein. That results from acute immunologic injury. Eg Aschoff bodies in RHD,  Rheumatoid nodule, hypertensive vasculitis etc.

Gangrene-

1. it is the gross necrosis of a large tissue.

Dry gangrene- coagulative necrosis

Wet gangrene- liquefactive necrosis

Apoptosis

• Programmed cell death without inflammation.

Morphology:

• Cell shrink
• Nuclear condensation 
• Nuclear fragmentation
• Cellular fragmentation into apoptotic bodies 
• Phagocytosis

Pathway 

• Intrinsic
• Extrinsic 

Examples of apoptosis 

Physiological 

• Organogenesis 
• Menstruation
• Lymphocytes in the thymus 

Pathological 

• Viral hepatitis- councilman bodies
• Cystic fibrosis- pancreas atrophy

Serum markers 

• When the cells die, their enzyme comes out and level can be detected in the blood.
• This gives an important clue for the diagnosis of the disease.

Common markers are

• AST and ALT
• CKMB
• Amylase and lipase
• LDH
• Myoglobin 

Tissue adaptation to injury 

Atrophy 

• Decrease in organ size due to decrease in the number and the size of each cell.

Cause of atrophy are

• Disuse due to immobilisation
• Denervation atrophy
• Lack of hormone stimulus
• Malnutrition 
• Aging

Picture:

• Decreased cellular components
• Autophagolysosomes 

Hypertrophy

• Increase it the organ size due to the increase of the cell size.

Causes:

• Increased Mechanical demand like weight lifters or in hypertension (cardiac hypertrophy)
• Increased hormone stimulation e.g. gravid uterus , lactating breast.

It occurs in response to

• Growth factors
• Cytokines
• They lead to increased expression of the concerned genes and then causing increased protein synthesis.

Hyperplasia

• Increase in the organ size because of the increase in the number of cells.

Cell types:

• Labile cells
• Stable cells
• Permanent cells 
• Only stable and permanent cells can undergo hyperplasia.

Eg:

• After hepatectomy, the liver gains full size. Breast development in puberty etc.
• The stimulus are similar the hyperplasia.

Metaplasia

• The reversible change of one cell type to another.
• It is in response to chronic irritation.

Examples are

• Squamos metaplasia of the bronchail epithelium in the smokers
• Barret’s  esophagus
• The new type of epithelium come from the reserve cells that lie in the basal layer.
• It is not premalignant, but chances of malignancy is as high as 10-15 times than the normal.

Dysplasia

• The loss of cell differentiation is called dysplasia.
• It is the hallmark of malignancy.
• It is characterized by changes in cell shape, size and differentiation.

Examples 

• Oral leukoplakia
• Cervical dysplasia
• Solar keratosis